PROJECT SUMMARY When the vocal fold (VF) lamina propria (LP) composition, geometry, and viscoelasticity are altered due to scarring, VF vibratory function can be severely disrupted, with resultant dysphonias ranging from hoarseness to voice loss. VF scarring has proven difficult to treat with current surgical techniques and standard augmentation substances (e.g., collagen, fat). Due to the size of the patient population suffering from voice impairment secondary to scarring, the development of augmentation materials optimized for the unique requirements of the LP is currently being actively investigated. We propose the systematic and quantitative assessment of specific material properties on VF fibroblast (VFF) behavior towards rational implant design. Our underlying premise is that in order to rationally develop a designer material suitable for restoration of scarred LP, we need to understand not only if the material meets the unique mechanical property environment of the LP but also the impact of critical material design parameters on VFF extracellular matrix production and phenotype. Specifically, the response of VFFs to a number of material parameters, such as pore size, biochemical stimuli, and degradation rate, can be successfully assayed in vitro and will form the basis of this proposal. The results can then used to guide the design of materials and to pre-screen materials for in vivo trials. We will employ a series of controlled, systematic modifications of a base material formed from diacrylate-derivatized poly(ethylene glycol) (PEGDA) macromers. Importantly, PEGDA hydrogels are intrinsically resistant to protein adsorption, resulting in a biological [unreadable]blank slate[unreadable] which can be modified in a controlled manner to contain defined biochemical stimuli. In addition the pore size and degradation rate of PEGDA hydrogels can be systematically modified, making PEG-based materials ideal for systematic material property-cell response investigations. PROJECT NARRATIVE Chronic voice impairment secondary to vocal fold (VF) lamina propria (LP) scarring can be debilitating in terms of quality of life and has proven difficult to treat with current surgical paradigms, with the result that alternate treatments such as designer biomaterial implants are being actively investigated. We propose to conduct controlled in vitro tissue engineering (TE) experiments for and quantitative assessment of specific material properties on vocal fold fibroblast cell behavior toward the rational systematic design of LP restoration materials. This proposed uncoupled investigation of alterations in material property inputs on cell behavior is unique in its design and has significance for a range of tissue regeneration applications.